Abstract
Both IDH1 mutation and MGMT promoter methylation are associated with longer survival. We investigated the ability of imaging correlates to serve as noninvasive biomarkers for these molecularly defined GBM subtypes. MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. IDH1 mutational and MGMT promoter methylation status were determined by DNA sequencing and methylation-specific PCR, respectively. Overall survival was determined by using a multivariate Cox model and the Kaplan-Meier method with a log rank test. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features. MGMT promoter methylation and IDH1 mutation were associated with longer median survival. Edema levels stratified survival for methylated but not unmethylated tumors. Median survival for methylated tumors with little/no edema was 2476 days (95% CI, 795), compared with 586 days (95% CI, 507-654) for unmethylated tumors or tumors with edema. All IDH1 mutant tumors were nCET positive, and most (11/14, 79%) were located in the frontal lobe. Imaging features including larger tumor size and nCET could be used to determine IDH1 mutational status with 97.5% accuracy, but poorly predicted MGMT promoter methylation. Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation. Edema stratifies survival in MGMT promoter methylated but not in unmethylated tumors; patients with methylated tumors with little or no edema have particularly long survival.
Highlights
AND PURPOSE: Both IDH1 mutation and MGMT promoter methylation are associated with longer survival
MGMT promoter methylation and IDH1 mutation were associated with longer median survival
Imaging features are potentially predictive of IDH1 mutational status but were poorly correlated with MGMT promoter methylation
Summary
MR imaging from 202 patients with GBM was retrospectively assessed for nonenhancing tumor and edema among other imaging features. A logistic regression model followed by ROC analysis was used to classify the IDH1 mutation and methylation status by using imaging features. Of the 202 patients, 96 had gross total resection, 94 had subtotal resection, and 12 had biopsy only (based on standard imaging) Cases included those associated with a previously published study.[26] Follow-up scans were obtained at approximately 4- to 6-week intervals. A test of the proportional hazards assumption was used after fitting a multivariate Cox model, which included MR imagingϪderived imaging features, MGMT promoter methylation status, IDH1 mutation status, age, and the corresponding 95% CIs were generated. The Kaplan-Meier method with the log rank test was used to estimate overall survival on the basis of MGMT promoter methylation status ( stratifying by nCET and edema) and IDH1 mutation status. Statistical analysis was performed with STATA (StataCorp, College Station, Texas)
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